Australian Pharmacist Newsletter – Vol.30, No. 12, December 2011

Combination use of methotrexate and non-steroidal anti-inflammatory drugs

Methotrexate is a disease modifying anti-rheumatic drug (DMARD) widely used for the treatment of rheumatoid arthritis, psoriasis and other systemic rheumatic disorders. Non-steroidal anti-inflammatories (NSAIDs) are frequently used in combination with methotrexate to provide symptomatic pain relief. NSAID therapy may be prescribed, or purchased overthe-counter on advice from a medical practitioner.

There have been reports of methotrexate toxicity associated with concurrent use of NSAIDs . Methotrexate is predominantly cleared unchanged by renal excretion. NSAIDs can decrease renal perfusion, and cause a rise in serum methotrexate levels with the potential for toxicity.

Methotrexate is also strongly protein bound, and may be displaced by NSAIDs. The risk of toxicity with concurrent use of NSAIDs appears to be dose-related. The risk is lowest in patients taking low doses (7.5–25 mg once weekly) used in the management of rheumatoid arthritis and psoriasis, and patients with normal renal function. The risk of toxicity is increased in patients taking high-dose methotrexate (e.g. for treatment of neoplastic diseases) and in those with renal impairment.

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Australian Pharmacist Newsletter – Vol.30, No. 12, December 2011